Noroviruses are a group of enteropathogenic viruses belonging to the taxonomic family Caliciviridae, which causes approximately 90% of epidemic non-bacterial outbreaks of gastroenteritis around the world and may be responsible for 50% of all foodborne outbreaks of gastroenteritis in the US. In developing countries, according to a 2008 estimate by CDC researchers, up to 200,000 children less than 5 years old die of norovirus infection each year. There is no vaccine against norovirus and no specific antiviral drugs to treat infections. To be safe and effective a vaccine must protect humans against two serotypes of Norovirus currently causing epidemics. Nanotherapeutics and its collaborators propose to conduct BLA-enabling preclinical development of a stable, dry-powder nasal norovirus vaccine that will form the basis for initiation of Phase I clinical studies. The vaccine consists of the GelVac" dry powder formulation in combination with recombinant virus-like particle (rVLP) antigens of two dominant norovirus genotypes (G-III) manufactured in green plants using a transient viral expression system. The powder vaccine is packaged in an established disposable nasal powder inhaler (Valois Monopowder MK IV) ready for nasal administration. The GelVac" dry-powder formulation is a novel in situ gelling nasal powder vaccine delivery platform based on GelSite(R) polymer, a distinct and inert ionic polysaccharide (polygalacturonic acid) that enhances the immune response through (1) prolonged nasal residence, (2) sustained antigen release by an in situ gelation mechanism, and (3) stabilization of vaccine antigens. The GelVac" dry powder approach addresses the storage and administration shortcomings of the current NoV oral approach. The G-I VLP antigen produced using the plant expression system has been successfully formulated with GelVac" dry powder and a series of preclinical immunogenicty studies have been conducted with the vaccine formulation at Arizona State University's (ASU). These studies have demonstrated that the antigen is stable in the GelVac" dry powder and nasal administration of the GelVac" dry powder with G-I antigen induced strong mucosal and humroal responses, including a robust IgA response in intestinal tract. In addition, the response levels generated with GelVac" dry powder was comparable or better than those with formulations containing a variety of TLR agonists as adjuvants. These studies formed a solid basis for the proposed fast-track development of GelVac" dry powder NoV vaccine containing both G-I and G-II antigens that is designed to provide protection against two dominant norovirus genotypes. PUBLIC HEALTH RELEVANCE: Noroviruses are a group of enteropathogenic viruses belonging to the taxonomic family Caliciviridae, which causes approximately 90% of epidemic non-bacterial outbreaks of gastroenteritis around the world and may be responsible for 50% of all foodborne outbreaks of gastroenteritis in the US. The GelVac" dry-powder formulation is a novel in situ gelling nasal powder vaccine delivery platform based on GelSite(R) polymer, a distinct and inert ionic polysaccharide (polygalacturonic acid) that enhances the immune response through (1) prolonged nasal residence, (2) sustained antigen release by an in situ gelation mechanism, and (3) stabilization of vaccine antigens. These studies formed a solid basis for the proposed fast-track development of GelVac" dry powder NoV vaccine containing both G-I and G-II antigens that is designed to provide protection against two dominant norovirus genotypes.